Prevalence of Thyroid Dysfunction and Autoimmunity among Pregnant Women with Gestational Diabetes Mellitus

important during pregnancy.


Introduction
Pregnancy involves complex hormonal changes.Gestational Diabetes Mellitus (GDM) and thyroid disease are the two most commonly encountered endocrine conditions during this time, often coexisting to varying degrees [1].
As reported by the International

Association of Diabetes in Pregnancy Study
Group, the occurrence of GDM can reach up to 17.5%.Concurrently, thyroid dysfunction, which may present as either hypothyroidism or hyperthyroidism, impacts 10-15% of women during the initial half of their pregnancy [2].
In countries where iodine is plentiful, the size of the thyroid gland increases by about 10% during pregnancy; in areas where iodine is scarce, this increase can reach 20%-40%.As a result, the production of thyroxin (T4) and triiodothyronine (T3) increases significantly-by about 50%-and the daily requirement for iodide also increases by 50% [3].
Pregnancy may occasionally result in the diagnosis of additional thyroid conditions that require treatment, such as thyroid cancer and nodular disease.
Pregnancy-related hormonal and metabolic changes include altered thyroid metabolism and elevated iodine levels in the urine.For example, the human chorionic gonadotropin hormone stimulates thyroid-stimulating hormone [4].As an effect, TSH tends to decrease while an elevation is seen on T4 and T3 levels [5].
The reasons for the change in thyroid functions during pregnancy include elevated thyroid metabolism, elevated plasma volume, increased renal iodine excretion, an increase in estrogen levels, and the corresponding production of thyroid-binding globulin (TBG) [6].
Thyroid hormone, central to human metabolism and neural development, also supports fetal brain growth via maternal transfer [7].

Thyroid Peroxidase Antibody
(TPOAB) positivity rates among pregnant women at 16 weeks gestation are approximately 10%, which is consistent with overall population levels.It has been suggested that the presence of TPOAB during pregnancy is strongly linked to an increased risk of developing postpartum thyroiditis and may be linked to hypothyroidism [8].

Subjects
With

Sample size and intended population
Regardless of their gravidity status, pregnant women who met the eligibility requirements were the target population and attended the obstetrics and gynecology outpatient department.

Sample size
G*Power was used to calculate the sample size, and the effect size was estimated to be 0.7 based on the study by Yanachkova & Kamenov (2021), who wanted to find out whether there were abnormalities in thyroid hormone levels in pregnant women with gestational diabetes [9].
We used a priori analysis software to calculates the independent sample t-test difference between two independent means (two groups).90% power was estimated for a sample size of 114 participants, consisting of 57 cases and 57 matched controls.A 10% dropout rate during follow-up and an error probability of 0 points.
According to this calculation, the study included two matched groups:  Group 1: 57 pregnant women with singleton pregnancies, GDM, ages >18, and between 24 and 37 weeks of gestation who provided informed consent to be included in the study (sample size).
 Group 2: an equivalent number of expectant mothers with a typical 75 g OGTT and a singleton pregnancy (57) in a ratio of 1:1 was chosen in the control group.

Methods
We

Statistical Methods
The was calculated with a 95% confidence interval.
There was no predictive ability at 0 points and a full predictive value at 1 point on the AUC scale.Pearson's correlation analysis assessed the linear relationship between thyroid profile measures and other parameters in women with GDM.Only significant correlations with P <0.05 were plotted on correlation graphs.There was a 5% margin of error accepted and a 95% confidence interval set.

Discussion
Age is recognized as a factor that elevates the risk of GDM, a finding corroborated by our research.The average age of women with GDM in this study was 30 years, with a standard deviation of 4.4 years, aligning with findings from other research [4,7,10].
A significant correlation was observed between GDM patients and a positive family history of diabetes indicating a higher prevalence of such a history in our sample compared to similar studies [11].Moreover, Yang et al. (2016) highlighted that the likelihood of GDM increases with age and is more prevalent among those with a familial diabetes history [12].
While not statistically significant, GDM patients tended to have higher mean TSH levels, whereas their mean FT4 levels were significantly lower, and TPO-Ab levels were higher compared to healthy pregnant women.
In a recent investigation carried out at a tertiary care facility involving 150 pregnant participants, divided equally between those diagnosed with GDM) and those without, findings revealed elevated TSH levels and antithyroid peroxidase (anti-TPO) levels in the GDM group compared to their non-GDM counterparts.Furthermore, the study observed that free thyroxine (FT4) levels were significantly reduced in women with GDM (p ≤0.001).This study encompassed a cohort of 150 women who were between 24 and 28 weeks into their pregnancy [11].
A retrospective case-control study analyzing the medical records of 662 pregnant women revealed elevated TSH and FT3 levels and a higher FT3:FT4 ratio in GDM patients [9].
One more comparable study by In contrast, our study found mean FT4 was significantly higher in the GDM group compared to controls (p =0.023).While the previous study showed no thyroid hormone level differences between GDM and controls, ours demonstrated elevated FT4 levels associated with gestational diabetes [14].
Our results also contrast with the studies by Agarwala et al. (2018) and Ruas et al. (2007) showing comparable FT4 and TSH values between GDM and healthy pregnancies.The high prevalence of iodine deficiency in our baseline study population may explain this discrepancy.While those studies found no thyroid level differences between groups, the iodine deficiency in our cohort may have contributed to the altered thyroid hormones we observed linked to gestational diabetes [15,16].
Our study demonstrates that low FT4 is an independent risk factor for GDM, evidenced by the statistically significant inverse linear correlation found between FT4 levels and blood glucose.As FT4 increased, the incidence of GDM gradually decreased.A prior study of 2,751 mothers also identified low FT4 as a predictor of GDM risk, with GDM incidence declining as FT4 rose, while TSH and TPO-Ab did not predict GDM.These findings suggest low FT4 confers risk for developing GDM, consistent with our current results.Thyroid hormones play a key role in glucose metabolism.Recent research shows maternal free T3 (FT3) correlates directly with BMI in pregnancy, while FT4 correlates inversely with BMI. 17 Higher FT4 was associated with increasing BMI and FT3, further elevating GDM risk in those with obesity [18].
However, in euthyroid pregnancies, a lower level of FT4 was associated with an increase in the ratio between FT3/FT4 levels and BMI, indicating an increase in peripheral deiodinase activity.This finding was reported in another study [19].Research has additionally demonstrated that excessive energy intake increases the rate at which peripheral T4 is transformed into T3, indicating that energy intake influences peripheral deiodinase activity [20].The results of all the aforementioned studies demonstrate the correlation between diabetes and low FT4 levels, which our study also supported.
TPO Ab-positivity is defined in terms of a specific TPO Ab concentration, which is defined in preparation kits.According to several studies, TPO Ab positivity (as opposed to.A higher risk of GDM is linked to negativity [7,21,22] and Sub-clinical hypothyroidism may increase this risk even more [23]. The

Conclusion
In conclusion, in the comparative casecontrol research conducted, it was observed that the average serum TSH levels were elevated in patients with GDM compared to a healthy control group, although the difference did not reach statistical significance.Nonetheless, a statistically significant difference was noted with a p-value of less than 0.05.Furthermore, the analysis revealed that mean FT4 and anti-TPO antibody levels were higher among pregnant women diagnosed with GDM.Our study also identified a correlation suggesting that higher FT4 concentrations were associated with a decreased risk of developing GDM.No significant relationships were established between serum TPO-Ab and TSH levels and the status of GDM.Based on these outcomes, it is recommended that healthcare professionals consider monitoring for relatively lower concentrations of FT4 within the normal range as a preventive measure against GDM, instead of focusing solely on extremely high percentiles or evident low thyroid function.

Ethical approval and consent to participate:
Each participant in the study was given information about the procedures and their right to withdraw from the study at any time without explanation.All information submitted would be treated with confidentiality, and participants would be assured of their anonymity.Necessary administrative rules were followed.The research ethical committee (REC) of the Fayoum University Faculty of Medicine approved the work ethically before it started.

Funding:
The authors have no sources of funding to declare for this manuscript.

Competing interests:
The authors declare no conflicts of interest.
performed an anthropometric height and weight assessment along with a thorough clinical examination, focusing on the signs and symptoms of hypothyroidism, obstetric history, family history of diabetes mellitus, and clinical examination.If there was any disparity between fundal height and the Last Menstrual Period (LMP) or if the LMP was uncertain, ultrasonography was conducted to determine the individual's gestational age.To diagnose and rule out GDM, the Oral Glucose Tolerance Test (OGTT) was utilized.Should any of the following plasma glucose levels have been surpassed, a diagnosis of GDM would have been made.The testing criteria for Pregnancy Plasma Glucose (PPG) were as follows:  Fasting plasma glucose > 92 mg/dL. 1 st -hour.PPG > 180 mg/dL. 2 nd -hour.PPG > 153 mg/dL.Thyroid Peroxidase Antibody (TPO), TSH, and T4 levels were measured in 5 ml of venous blood extracted from the cubital vein of pregnant women enrolled in the study.As per the 2014 American Thyroid Association (ATA) guidelines, a normal serum FT4 level (standard reference range 9-23 mIU/ml) and a TSH between 3 and 10 mIU/ml are considered subclinical hypothyroidism.Apparent hypothyroidism was defined as either a TSH value ≥ 10 mIU/L independent of the FT4 value or a TSH > 3 mIU/L with a combination with a reduced FT4.Clinical hyperthyroidism was diagnosed when there was an elevated FT4 and a suppressed or undetectable serum TSH.Thyroid peroxidase antibodies (TPA) were considered positive if the titer exceeded the upper limit of the standard reference range (<35 IU/mL).

Figure 1 :
Figure 1: Comparison of Blood Glucose Tests between Both Study Groups.

Table 1 :
Study parameters related to both groups' demographics and obstetrics (N= 114).
Data is presented as Mean ±SD or Median (IQR).aIndependentsamplet-test;Mann-WhitneyU test; c Chi-Square test.*Statisticallysignificant.The blood glucose test results for the two groups under study are compared in Table2and Figure1.When comparing the blood glucose levels of GDM women to those of healthy controls, there was a significant difference in both the 1 st and 2 ndhour postprandial blood glucose (p <0.001), as well as in fasting blood glucose.

Table 2 :
Comparison of the two groups under study's blood glucose tests (N= 114).

Table 3 and
Figure 2 present a

Table 3 :
Comparison of Thyroid profile between both Study groups (N= 114).

Table 4 :
Correlation analysis between Thyroid profile tests and other studied variables among studied GDM pregnant women (N= 57).

Table 5 :
Results of ROC curve analysis for sensitivity and specificity of TSH, FT4, and TPO-AB as indicators and diagnostic predictors for GDM(N= 114) AUC: Area under the curve, CI: Asymptotic 95% Confidence Interval of AUC, FT4: free Thyroxine; TSH: Thyrotropin; TPO-Ab, Thyroid Peroxidase Autoantibodies.